REGULATION OF ANF RELEASE FROM A HEART-LUNG PREPARATION

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Recent studies suggest that the atrial natriuretic factor (ANF) is a circulating hormone that may be involved in the regulation blood volume and arterial pressure but little is known concerning the physiological regulation of ANF secretion. One factor which has been shown to release ANF is an increase in atrial stretch or volume. It is important to determine what other factors influence ANF secretion and whether these factors have a direct effect on ANF release or act by modulating the ANF response to atrial distension. For this purpose, a rat heart-lung preparation has been developed in which both venous return and aortic pressure can be regulated and ANF measured directly from the perfusion reservoir by radioimmunoassay. The specific aims of this project are 1) to determine if increases in perfusate sodium concentration have a direct effect on ANF release, 2) to determine if angiotensin II or ADH have a direct negative feedback effect on ANF secretion, 3) to examine the effect of an increase in cardiac afterload on ANF release with venous return held constant, 4) to determine the direct effect of alpha or beta adrenergic receptor stimulation on ANF release under conditions where aortic pressure and venous return are held constant and 5) to test the hypothesis that dopamine plays a role in ANF secretion. It is hypothesized that ANF plays a role in the control of plasma sodium concentration and that angiotensin II and ADH, which are released under conditions of reduced blood volume, will have an inhibitory effect on ANF secretion. Increases in cardiac afterload should increase ANF release by increasing atrial pressure. Although some work suggests that adrenergic stimulation increases ANF release in vivo, it is possible that beta or alpha adrenergic stimulation has a direct inhibitory effect on ANF secretion. Since dopamine antagonists attenuate the natriuresis and hypoaldosteronism produced by volume expansion, it is predicted that dopamine plays a role in ANF release from the heart. These studies will be important in our understanding of the physiological role of ANF in body fluid balance.